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Results of combined pulmonary resection and cardiac operation
Results of Combined Pulmonary Resection and Cardiac Operation Vivek Rao, MD, Thomas R. J. Todd, MD, Richard D. Weisel, MD, Masashi Komeda, MD, PhD, Gideon Cohen, MD, John S. Ikonomidis, MD, PhD, and George T. Christakis, MD Divisions of Thoracic and Cardiovascular Surgery,, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada
Background. Concomitant lesions of the heart and lung are u n c o m m o n , but w h e n present they pose a therapeutic challenge for thoracic surgeons. A combined procedure avoids the need for a second major thoracic procedure and may improve outcomes and provide economic benefit. However, cardiopulmonary bypass may adversely affect the natural history of pulmonary malignancies. Methods. The clinical records of 30 patients were reviewed w h o underwent simultaneous lung resection and cardiac operations b e t w e e n January 1982 and July 1995. Follow-up was obtained on all 30 patients (mean follow-up, 22 months; range, 1 to 100 months). Results. Twenty-four patients underwent coronary artery bypass grafting in conjunction with pulmonary resection. Six patients underwent aortic (n = 4) or mitral (n = 2) valve replacement. The pulmonary resections consisted of p n e u m o n e c t o m y (n = 3), lobectomy (n = 14), w e d g e excision (n = 12), and tracheal resection (n = 1). Twenty-one patients had pathologic findings that con-
firmed adenocarcinoma (n = 10), squamous cell carcinoma (n = 5), small cell carcinoma (n = 2), or other malignancy (n = 4). Tumor stage of primary lung cancers was stage I, n = 12; stage II, n = 3; and stage IIIa, n = 2. Pathologic examination revealed benign disease in 9 patients. There were two operative deaths, one due to aspiration and one due to stroke. There were three late deaths, two cardiac and one of metastatic disease. Overall late survival was 85% ± 7% and 73% + 16% at 1 and 5 years, respectively. Actuarial survival for patients with malignant disease was 64% at 5 years. Conclusions. Simultaneous cardiac operation and lung resection was not associated with increased early or late morbidity or mortality. Cardiopulmonary bypass does not adversely affect survival in patients with malignant disease. Cardiac valve replacement can be performed safely in conjunction with pulmonary resection.
oncomitant lesions of the heart and lungs are uncommon, but when present they pose a therapeutic d i l e m m a to the cardiothoracic surgeon. Most patients p r e s e n t with coronary artery or other cardiac disease and are found to have an a s y m p t o m a t i c p u l m o n a r y lesion on their preoperative chest roentgenogram. Less frequently, patients with lung cancer are found to have substantial cardiac disease which, if untreated, greatly increases the perioperative m o r b i d i t y and mortality of p u l m o n a r y resection [1, 2]. Surgeons m a y be reluctant to perform a one-stage simultaneous p r o c e d u r e because of concerns regarding systemic h e p a r i n administration or operative exposure through a m e d i a n s t e r n o t o m y [3, 4]. However, a one-stage c o m b i n e d p r o c e d u r e avoids the need for a second major thoracic procedure, m a y reduce overall hospital stay, and m a y result in economic benefit. The early results of c o m b i n e d cardiac operation and p u l m o n a r y resection have been encouraging [5-11]. Alt h o u g h a c o m b i n e d operation has p r o v e n to be a technical success, the relatively small n u m b e r of patients who
have both cardiac disease and lung cancer has m a d e it difficult to study the long-term results of the c o m b i n e d procedure. In addition, the long interval r e q u i r e d to accumulate enough experience with c o m b i n e d operation has resulted in a confounding of results because of changes in operative technique or perioperative m a n a g e m e n t of lung cancer. The long-term prognosis is particularly i m p o r t a n t in considering lung cancer, as the use of c a r d i o p u l m o n a r y bypass (CPB) is known to have several systemic effects [12-16]. The immunologic consequences of CPB a n d their effects on the long-term prognosis of patients with lung cancer are not well u n d e r s t o o d [17]. This study describes a 14-year experience with comb i n e d lung resection a n d cardiac operation at The Toronto Hospital. We compare the results of lung resection for m a l i g n a n t disease versus benign disease in an att e m p t to characterize the effect of CPB on the long-term prognosis of patients with lung cancer.
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(Ann Thorac Surg 1996;62:342-7)
Material and Methods Presented at the Third-second Annual Meeting of The Society of Thoracic Surgeons, Orlando, FL, Jan 29-31, 1996. Address reprint requests to Dr Weisel, Division of Cardiovascular Surgery, EN 14-215,The Toronto Hospital, 200 Elizabeth St, Toronto, Ontario M5G 2C2, Canada. © 1996 by The Society of Thoracic Surgeons Published by Elsevier Science lnc
We reviewed the clinical records of all patients who u n d e r w e n t p u l m o n a r y resection and cardiac operation requiring extracorporeal circulation b e t w e e n January 1, 1982 and July 1, 1995. Patients who u n d e r w e n t single or 0003-49751961515.00 Pll S0003-4975(96)00349-9
A n n Thorac Surg 1996;62:342-7
double lung transplantation necessitating CPB (n = 69) were excluded. Follow-up data were collected at the thoracic surgery postoperative clinics a n d were complete for all patients. Follow-up r a n g e d from 1 to 101 m o n t h s (mean, 29 months).
Operative Technique Mediastinoscopy was p e r f o r m e d at the b e g i n n i n g of the operative p r o c e d u r e in 16 of the 18 patients who presented p r e o p e r a t i v e l y with a b n o r m a l chest roentgenograms or with a known diagnosis of malignancy. No N2 disease was f o u n d in any of these 16 patients. The p u l m o n a r y resection was p e r f o r m e d before the institution of CPB in 4 patients, d u r i n g CPB in 19 patients, and after reversal of h e p a r i n t r e a t m e n t in 7 patients. In 23 patients, the cardiac p r o c e d u r e was c o m p l e t e d before the lung resection. Postoperative care was uniform in all patients. Two patients received adjuvant c h e m o t h e r a p y after lung resection. Both of these patients h a d a diagnosis of small cell carcinoma.
Statistical Analysis Statistical analysis was p e r f o r m e d with the BMDP statistical p r o g r a m (BMDP Statistical Software, Los Angeles, CA). Categoric data were evaluated using X2 analysis or Fisher's exact test as appropriate. Continuous variables were analyzed using analysis of variance. Actuarial survival was d e t e r m i n e d using the K a p l a n - M e i e r m e t h o d [18]. The generalized Wilcoxon test was u s e d to c o m p a r e survival b e t w e e n groups. Statistical significance was ass u m e d at p less than 0.05.
Results
Preoperative Data The m e a n age of the 30 patients was 61 + 13 years (range, 17 to 79 years). There were 26 m e n and 4 women. Left ventricular ejection fraction was greater than 0.60 in 9, 0.40 to 0.59 in 16, 0.20 to 0.39 in 5, a n d less than 0.20 in none. T u m o r stage (primary lung cancer) was stage I in 12, stage II in 3, a n d stage IIIa in 2. Other malignancies were p r e s e n t in 4 patients. A b n o r m a l p r e o p e r a t i v e chest r o e n t g e n o g r a m s were detected in 18 patients who p r e s e n t e d with cardiac complaints. Seven patients with known p u l m o n a r y neoplasms were discovered to have substantial u n d e r l y i n g coronary artery disease on the basis of history, and physical examination. These patients s u b s e q u e n t l y und e r w e n t exercise stress tests or thallium scanning before coronary a n g i o g r a p h y a n d consideration of simultaneous coronary revascularization. O n e patient p r e s e n t e d with h e m o p t y s i s and was found to have a tracheal n e o p l a s m and two-vessel coronary artery disease. Four patients u n d e r w e n t cardiac operation a n d h a d p u l m o n a r y lesions detected intraoperatively; the p u l m o n a r y lesion was found to be a benign g r a n u l o m a or e m p h y s e m a t o u s bleb.
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343
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Operative Data The average aortic cross-clamp time was 54 - 21 m i n u t e s (range, 23 to 106 minutes), and CPB time was 109 + 34 minutes (range, 38 to 158 minutes). The p u l m o n a r y resection consisted of p n e u m o n e c t o m y in 3 patients (10%), lobectomy in 14 (47%), w e d g e resection in 12 (40%), and tracheal resection in I (3%). Twentyfour patients received one or more coronary artery bypass grafts (one in 1, two in 6, three in 10, four in 5, and m o r e than four in 2). Six patients h a d either an aortic (n = 4) or mitral (n = 2) valve replacement. Right or left atrial resection was r e q u i r e d in 2 patients. One patient required a right atrial resection a n d right u p p e r lobe w e d g e resection for metastatic renal cell carcinoma, a n d the second patient r e q u i r e d a left atrial resection for m y x o m a c o m b i n e d with a right lower lobectomy for a metastatic chondrosarcoma. Pathologic examination revealed a malignant lesion in 21 patients: a d e n o c a r c i n o m a (n = 10), s q u a m o u s cell carcinoma (n = 5), small cell carcinoma (n = 2), metastatic renal cell carcinoma (n = 3), a n d metastatic chondrosarcoma (n = 1). The majority of patients (n = 12, 57%) p r e s e n t e d with stage I disease. Two patients were found to have N2 disease at thoracotomy despite negative m e d i a s t i n o s c o p y results. These patients are both alive and disease free at 2 a n d 3 years, respectively. Benign lesions were excised in 9 patients (granulomata or e m p h y s e m a t o u s bleb) (Fig 1). There were two operative deaths. One patient suffered a perioperative stroke and died on postoperative day 15; the second patient died on postoperative day 5 of massive aspiration. Prolonged ventilation (>24 hours) was r e q u i r e d for 4 additional patients, who were all discharged home in satisfactory condition. Only I patient r e q u i r e d r e o p e n i n g for persistent chest tube drainage. This patient had u n d e r g o n e a tracheal resection and double coronary artery bypass. No source of b l e e d i n g was identified at reexploration. One patient suffered a p u l m o n a r y e m b o lus on the third postoperative day. This patient experienced a second p u l m o n a r y e m b o l u s with resultant respiratory arrest. This patient received an inferior vena caval
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filter and was eventually discharged home on the 26th postoperative day. One patient who had received five coronary artery bypass grafts and underwent right upper lobectomy required a permanent pacemaker for thirddegree heart block. There were no perioperative myocardial infarctions. The postoperative length of stay for all patients was 12.1 + 7.6 days (median, 10 days; range, 4 to 25 days). For those patients who were discharged from the hospital, the average length of stay was 12.5 +_ 7.8 days (median, 10 days; range, 5 to 25 days).
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There were three late deaths: Two patients died of fatal myocardial infarctions and the third patient died of recurrent malignant disease. Overall actuarial survival was 85% _+ 7% at I year, 85% -+ 7% at 5 years, and 61% _+ 21% at 7 years (Fig 2). Figure 3 compares patients who underwent lung resection for benign disease and those who were found to have a malignant lesion. There was only one death in a patient with benign disease. This patient suffered a fatal myocardial infarction 7 years after bypass operation. There were two late deaths in patients with malignant disease. One patient with metastatic chondrosarcoma presented 3 months after operation with an intracranial lesion and died after an intracerebral hemorrhage. The second patient suffered a fatal myocardial infarction 3 months after bypass. There were 3 patients who developed recurrent disease, but all 3 were alive at follow-up. Of the 2 patients with small cell carcinoma, both were alive and disease free at 2 and 5 years, respectively.
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disease may significantly increase the morbidity of pulmonary resection [1]. In addition, a two-stage procedure has the disadvantages of two anesthetics, two incisions, and a longer overall hospital stay. A single combined procedure may therefore be preferred, with potential economic benefit. Pulmonary resection through a median sternotorny has been shown to result in excellent outcomes [3, 4]. Although the technical feasibility of a simultaneous procedure has been well demonstrated in several small series [5-11], the lack of long-term follow-up in a large series of patients makes it difficult to determine the long-term outcomes of the combined procedure. T h e Effect o f C a r d i o p u l m o n a r y B y p a s s
Cardiopulmonary bypass has been shown to produce several systemic side effects [12-16]. The immunologic effects of CPB are of concern in patients with malignant disease. Cardiopulmonary bypass is known to affect neutrophils and platelets and to result in complement activation. This inflammatory stimulation may be of benefit in patients with malignancies. However, attempts to resect neoplasms during CPB may lead inadvertently to systemic seeding of malignant cells. Blood transfusion is associated with an increased risk of recurrence. In addition, there is a potent immunosuppressive effect of CPB, which may be detrimental to the long-term prognosis of patients with malignancies. A report by Canver and associates [17] demonstrated that cardiac operation in patients with a previously resected cancer gave acceptable results, with a 96% 3-year survival. However, only 1 patient in this series of 46 had a diagnosis of lung cancer. In addition, all patients in this series had undergone a previous "curative" resection of their malignancy and thus, their tumor burden was minimal at the time of cardiac operation. A study by Ulicny and co-workers [9] examined the results of concomitant cardiac and pulmonary procedures. In this series of 19 patients, the authors found a 5-year survival
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of only 40% in patients with m a l i g n a n t disease, c o m p a r e d with 75% in patients found to have a benign p u l m o n a r y lesion. A similar result was obtained in a larger series r e p o r t e d by Brutel de la Riviere a n d colleagues [10]. In a group of 79 patients who u n d e r w e n t a c o m b i n e d procedure over a 15-year period, the overall survival at 5 years was 42%. The authors found that the 5-year survival was higher in patients who u n d e r w e n t lung resection before CPB (55%) versus those who u n d e r w e n t lung resection after CPB (20%). Unfortunately, this difference failed to achieve statistical significance because of the small n u m ber of patients available for analysis at 5 years. Nevertheless, these results do suggest a potential d e t r i m e n t a l effect of CPB. A r e p o r t by N a r u k e and associates [19] d e m o n s t r a t e d that a m o n g stage I tumors, overall 5-year survival in n o n - s m a l l cell n e o p l a s m s was a p p r o x i m a t e l y 65%. O u r results in patients with malignant disease a p p e a r to be similar to those o b t a i n e d in patients with benign p u l m o n a r y lesions, with an overall 5-year survival of greater than 80%. Thus, it does not a p p e a r that CPB h a d a d e t r i m e n t a l effect on 5-year survival in our series. In addition, the p r e d o m i n a n t cause of late death in our series was cardiac, not recurrence of malignancy. Therefore, patients who u n d e r g o a c o m b i n e d p r o c e d u r e may be at risk for recurrence, but they are just as likely to die of progression of their cardiac disease.
Timing of Lung Resection The timing of the lung resection m a y be i m p o r t a n t for both early a n d late operative outcomes. In addition to the concern r e g a r d i n g systemic m e t a s t a s e s d u r i n g CPB, there is a d a n g e r of b l e e d i n g secondary to anticoagulation therapy. Ulicny and co-workers [9] e x a m i n e d the role of CPB in c o m b i n e d operations and concluded that lung resection during CPB was associated with excessive b l e e d i n g and p u l m o n a r y complications. These authors r e c o m m e n d e d resection after reversal of anticoagulation with p r o t a m i n e sulfate. In our series, 19 (63%) of the patients u n d e r w e n t resection d u r i n g CPB, and only 1 patient suffered from a b l e e d i n g complication requiring reexploration. O u r p r e f e r r e d a p p r o a c h to the stable patient is to perform a preoperative staging mediastinoscopy. We then complete the cardiac p r o c e d u r e a n d remove the aortic cross-clamp. Resection of the p u l m o n a r y lesion is p e r f o r m e d during CPB. C a r d i o p u l m o n a r y b y p a s s facilitates resection of left lower lobe lesions through a m e d i a n sternotomy. Four patients in our series u n d e r w e n t lung resection before the institution of CPB. All 4 of these patients u n d e r w e n t w e d g e resections of p e r i p h e r a l tumors. Three of the 4 were found to have benign disease; the fourth patient was found to have an a d e n o c a r c i n o m a a n d p r o c e e d e d to formal right lower lobectomy after r e p l a c e m e n t of his aortic valve. Seven patients u n d e r w e n t p u l m o n a r y resection after discontinuation of CPB. If there is concern about the patient's ability to w e a n from CPB, we prefer to complete the cardiac p r o c e d u r e and decannulate. If the patient r e m a i n s stable after discontinuation of CPB, we proceed with the p u l m o n a r y resection.
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In patients u n d e r g o i n g valve operations, we prefer to resect the p u l m o n a r y lesion after closure of the pericard i u m to avoid contamination b y respiratory pathogens. In our small series of 6 patients, we did not observe any complications related to infective endocarditis. W e believe that our technique of pericardial closure partially protects against infection due to the presence of a transected airway.
Summary The early outcomes of c o m b i n e d p u l m o n a r y resection and cardiac operation have d e m o n s t r a t e d that this approach is both feasible a n d safe in carefully selected patients. The long-term results of concomitant operation are less well defined because of the lack of a large series of patients available for follow-up. In our series, late death was p r e d o m i n a n t l y r e l a t e d to cardiac causes, which suggests that the adverse effects of CPB on pulm o n a r y malignancies m a y not be an i m p o r t a n t factor w h e n considering a patient for a simultaneous procedure. W h e n faced with a patient with concomitant p u l m o nary a n d cardiac disease, we favor a single-stage comb i n e d procedure. The p u l m o n a r y resection is facilitated by CPB, and we have not o b s e r v e d any increased morbidity from anticoagulation therapy. If the cardiac procedure is difficult or the patient is unstable, the lung resection can be delayed. W e r e c o m m e n d closure of the p e r i c a r d i u m in patients u n d e r g o i n g simultaneous valve operation and lung resection to protect against contamination from a transected airway. In certain high-risk patients, separate staged procedures m a y be the most p r u d e n t course of action. However, in carefully selected patients with concomitant disease, a c o m b i n e d a p p r o a c h can be used with m i n i m a l perioperative morbidity and acceptable long-term results. This study was supported by the Heart and Stroke Foundation of Ontario (HSFO): Dr Rao is a Pharmaceutical Roundtable Fellow of the HSFO; Dr Weisel is a Career Investigator of the HSFO; Dr Cohen is a Surgical Scientist at the Department of Surgery, University of Toronto; and Dr Christakis is a Research Scholar of the HSFO. We thank Ms Joan Ivanov, RN, MSc, for her statistical expertise and assistance with the preparation of the manuscript.
References 1. Thomas P, Giudicelli R, Guillen JC, Fuentes P. Is lung cancer surgery justified in patients with coronary artery disease? Eur J Cardiothorac Surg 1994;8:287-92. 2. Rao TK, Jacobs KH, El-Err AA. Reinfarction following anaesthesia in patients with myocardial infarction. Anaesthesiology 1983;59:499-505. 3. Urschel HC Jr, Razzuk MA. Median sternotomy as a standard approach for pulmonary resection. Ann Thorac Surg 1986;41:130-4. 4. Cooper JD, Nelems JM, Pearson FG. Extended indications for median sternotomy in patients requiring pulmonary resection. Ann Thorac Surg 1978;26:413-9. 5. Piehler JM, Trastek VF, Pairolero PC, et al. Concomitant
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11. 12.
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cardiac and pulmonary operations. J Thorac Cardiovasc Surg 1985;90:662-7. Dalton ML, Parker TM, Mistrot JJ, Bricker DL. Concomitant coronary artery bypass and major noncardiac surgery. J Thorac Cardiovasc Surg 1978;75:621-4. Peters RM, Swain JA. M a n a g e m e n t of the patient with emphysema, coronary artery disease and lung cancer. Am J Surg 1982;143:701-5. Yokoyama T, Derrick MJ, Lee AW. Cardiac operation with associated pulmonary resection. J Thorac Cardiovasc Surg 1993;105:912-6. Ulicny KS Jr, Schmelzer V, Flege JB Jr, et al. Concomitant cardiac and pulmonary operation: the role of cardiopulmonary bypass. Ann Thorac Surg 1992;54:289-95. Brutel de la Riviere A, Knaepen P, Van Swieten H, Ernst J, Van den Bosch J. Concomitant open heart surgery and pulmonary resection for lung cancer. Eur J Cardiothorac Surg 1995;9:310-4. Canver CC, Bhayana JN, Lajos TZ, et al. Pulmonary resection combined with cardiac operations. Ann Thorac Surg 1990;50: 796-9. Christakis GT, Koch JP, Deemar KA, et al. A randomized
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13.
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15. 16. 17.
18. 19.
study of the systemic effects of warm heart surgery. Ann Thorac Surg 1992;54:449-59. Cavarocchi NC, Pluth JR, Schaff HV, et al. Complement activation during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1986;91:252-8. Moore FD, Warner KG, Assousa S, et al. The effect of complement activation during cardiopulmonary bypass. Ann Surg 1988;208:95-103. Butler J, Rocker GM, Westaby S. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1993;55:552-9. Colman RW. Platelet and neutrophil activation in cardiopulmonary bypass. Ann Thorac Surg 1990;49:32-4. Canver CC, Mazzin CAS, Plume SK, Nugent WC. Should a patient with a treated cancer be offered an open heart operation? Ann Thorac Surg 1993;53:1202-4. Kaplan EL, Meier P. Non-parametric estimations from incomplete observations. J Am Stat Assoc 1958;53:457-81. Naruke T, Goya T, Tsuchiya R, Suemasu K. Prognosis and survival in resected lung carcinoma based on the new international staging system. J Thorac Cardiovasc Surg 1988; 96:440-7.
DISCUSSION DR PETER C. PAIROLERO (Rochester, MN): I thank Dr Rao for his excellent presentation. The issue of compromised survival for patients with lung cancer after concomitant pulmonary and cardiac operations is not new. Peters first suggested this association as early as 1982, w h e n he suggested that alterations in the i m m u n e mechanism occurred after extracorporeal circulation that accelerated malignant disease. Since then, others, including our group, have suggested that it is less a matter of reduced immunocompetency and more a situation of incomplete cancer staging through a median sternotomy incision. In our series of 30 patients with lung cancer presented before this Society 2 years ago, overall 5-year survival after concomitant pulmonary and cardiac operations was 35%. This is in marked contrast to the 64% five-year survival reported in the present study for patients with malignant disease. Equally as important, survival in our concomitant patients was not significantly affected by the stage of the disease, even though more than 75% of our patients were presumed to have stage I disease. Our observation of reduced survival was also in marked contrast to the survival observed in another of our patient groups, who had cardiac operations followed by staged pulmonary resections for lung cancer within the following year. Five-year survival for our staged patients was 53%. Why the differences? Well, for one thing, the n u m b e r of patients in both the Toronto group and our group is small, and this could easily explain the differences. We, however, concluded that lymph node evaluation was not as complete in our patients undergoing concomitant operations because of the limitations of exposure imposed by the median sternotomy. In fact, we concluded that some of our stage I concomitant patients were actually occult stage IIL Recognizing the limitations imposed by sternotomy, Dr Rao suggested, and I entirely agree, that mediastinoscopy be performed before an elective cardiac operation in all patients with known lung cancer. But what about the patients found to have lung cancer during the cardiac surgical procedure? I would like to ask several questions. What does the Toronto group recomm e n d be done at the time of sternotomy to ensure adequate staging of the mediastinum if mediastinoscopy has not been
previously done? Specifically, how do they evaluate the subcarinal lymph nodes? The concern, of course, is that subcarinal lymph nodes are not sampled. Second, did their patients have lymphadenectomy or simply lymph node biopsy of the various stations? Their 5-year cancer survival of 64% is excellent and suggests a stage I disease pattern. This is even more significant w h e n you realize that 30% of their primary cancer patients had either stage Ii or stage III disease and that another 10% of their patients had small cell lung cancers. DR RAO: Dr Pairolero has raised a n u m b e r of important issues. First, there is the importance of the timing of the lung resection vis-a-vis the institution of cardiopulmonary bypass. A large European study by Brutel de la Riviere and associates examined 79 patients who underwent concomitant operations over a 15-year period. There was a small, statistically nonsignificant improvement in survival in those patients who underwent lung resection before cardiopulmonary bypass. Unfortunately, their series and ours lack the statistical power to detect a difference in survival if one exists. Their finding does raise a concern, however, about the possible detrimental effects of cardiopulmonary bypass on the long-term prognosis of these patients. The second point concerned the adequacy of preoperative staging during a combined procedure. Cervical mediastinoscopy is a routine procedure at our institution. Ideally, a patient who presents with concomitant disease is adequately staged preoperatively and intraoperatively. In the unfortunate event that a "surprise" lesion is found at cardiac operation, there are a n u m b e r of options. We prefer to perform a wedge excision for pathologic confirmation of malignancy. If the patient is unstable during the operation, we would complete the cardiac procedure and proceed with complete tumor staging postoperatively, with the potential for a second, staged procedure. Alternatively, if the patient is stable, we would proceed to open the posterior pericardium and mobilize the right pulmonary artery, allowing an extensive evaluation of the subcarinal space. If no nodal disease were found, we would complete a formal cancer resection as clinically indicated.
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DR WILLIAM MITCHEL SEE (Columbia, MO): Doctor Rao, you certainly have had very, good results. I am impressed that the distribution of stage I patients was very high relative to what we expect. In Missouri, we have performed 20 combined procedures and several that we staged, as Dr Pairolero suggested. One of the difficult problems I have that is not addressed in this study is the pleural space. We are still using cold cardioplegia and topical cooling, and nearly all of my patients have left lower lobe atelectasis. Their chest roentgenograms do not normalize for about 6 or 8 weeks. It has been a real problem for me in performing a lobectomy, which has its own space problems, directly after a cardiac operation, when you need to have all of the lung reexpanded. I also have been reluctant to pursue lower lobectomies simply because I am not in favor of performing them during cardiopulmonary bypass. Instead, I finish the cardiac operation and then, only if everything is perfect, will I consider an upper lobectomy. I would like to ask you about your pleural space problems. Does this combined lung resection and coronary artery bypass procedure dissuade you from using the internal mammary artery as a conduit? Do you try to stay out of that pleural space? D R RAO: We have found that topical cooling leads to an increased risk of phrenic nerve injury and diaphragmatic paral-
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ysis, which may predispose to pulmonary complications postoperatively. Our incidence of pleural space complications decreased significantly after we a b a n d o n e d the use of topical slush. Four patients had emphysematous lesions detected intraoperatively, which may have compromised the use of a m a m m a r y artery graft. These blebs were successfully removed with wedge excisions to allow proper placement of the left internal mammary artery. Thus, we do not believe that a combined procedure precludes the use of a m a m m a r y artery. D R SHAF KESHAVJEE (Toronto, Ontario, Canada): One of the
other options that we use for unexpected intraoperative findings is a diagnostic wedge resection. I believe that the low mortality and low morbidity results that Dr Rao reported reflect this clinical judgment. In the case of a complex valvular and bypass operation, for example, we would do a wedge resection of the lesion for diagnosis. W h e n the patient recovers from the cardiac procedure, we would bring him back for complete radiologic imaging and mediastinoscopy, followed by lung resection. We emphasize, however, that "unexpected" pulmonary pathologic findings can be avoided if the preoperative chest roentgenogram is reviewed.
Notice From The Thoracic Surgery Foundation for Research and Education I n f o r m a t i o n a b o u t a n d a p p l i c a t i o n s for 1996 R e s e a r c h Grants, Research Fellowships, and Career Development A w a r d s a r e n o w a v a i l a b l e . T h e d e a d l i n e for r e c e i p t of c o m p l e t e d a p p l i c a t i o n s is O c t o b e r 14, 1996. P l e a s e c o n tact A m y H e d m a r k to r e q u e s t a n a p p l i c a t i o n or f u r t h e r information.
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The Thoracic Surgery Foundation for Research and Education 401 North Michigan Avenue Chicago, IL 60611 Phone: (312) 644-6610 Fax: (312) 527-6635
Background. Concomitant lesions of the heart and lung are u n c o m m o n , but w h e n present they pose a therapeutic challenge for thoracic surgeons. A combined procedure avoids the need for a second major thoracic procedure and may improve outcomes and provide economic benefit. However, cardiopulmonary bypass may adversely affect the natural history of pulmonary malignancies. Methods. The clinical records of 30 patients were reviewed w h o underwent simultaneous lung resection and cardiac operations b e t w e e n January 1982 and July 1995. Follow-up was obtained on all 30 patients (mean follow-up, 22 months; range, 1 to 100 months). Results. Twenty-four patients underwent coronary artery bypass grafting in conjunction with pulmonary resection. Six patients underwent aortic (n = 4) or mitral (n = 2) valve replacement. The pulmonary resections consisted of p n e u m o n e c t o m y (n = 3), lobectomy (n = 14), w e d g e excision (n = 12), and tracheal resection (n = 1). Twenty-one patients had pathologic findings that con-
firmed adenocarcinoma (n = 10), squamous cell carcinoma (n = 5), small cell carcinoma (n = 2), or other malignancy (n = 4). Tumor stage of primary lung cancers was stage I, n = 12; stage II, n = 3; and stage IIIa, n = 2. Pathologic examination revealed benign disease in 9 patients. There were two operative deaths, one due to aspiration and one due to stroke. There were three late deaths, two cardiac and one of metastatic disease. Overall late survival was 85% ± 7% and 73% + 16% at 1 and 5 years, respectively. Actuarial survival for patients with malignant disease was 64% at 5 years. Conclusions. Simultaneous cardiac operation and lung resection was not associated with increased early or late morbidity or mortality. Cardiopulmonary bypass does not adversely affect survival in patients with malignant disease. Cardiac valve replacement can be performed safely in conjunction with pulmonary resection.
oncomitant lesions of the heart and lungs are uncommon, but when present they pose a therapeutic d i l e m m a to the cardiothoracic surgeon. Most patients p r e s e n t with coronary artery or other cardiac disease and are found to have an a s y m p t o m a t i c p u l m o n a r y lesion on their preoperative chest roentgenogram. Less frequently, patients with lung cancer are found to have substantial cardiac disease which, if untreated, greatly increases the perioperative m o r b i d i t y and mortality of p u l m o n a r y resection [1, 2]. Surgeons m a y be reluctant to perform a one-stage simultaneous p r o c e d u r e because of concerns regarding systemic h e p a r i n administration or operative exposure through a m e d i a n s t e r n o t o m y [3, 4]. However, a one-stage c o m b i n e d p r o c e d u r e avoids the need for a second major thoracic procedure, m a y reduce overall hospital stay, and m a y result in economic benefit. The early results of c o m b i n e d cardiac operation and p u l m o n a r y resection have been encouraging [5-11]. Alt h o u g h a c o m b i n e d operation has p r o v e n to be a technical success, the relatively small n u m b e r of patients who
have both cardiac disease and lung cancer has m a d e it difficult to study the long-term results of the c o m b i n e d procedure. In addition, the long interval r e q u i r e d to accumulate enough experience with c o m b i n e d operation has resulted in a confounding of results because of changes in operative technique or perioperative m a n a g e m e n t of lung cancer. The long-term prognosis is particularly i m p o r t a n t in considering lung cancer, as the use of c a r d i o p u l m o n a r y bypass (CPB) is known to have several systemic effects [12-16]. The immunologic consequences of CPB a n d their effects on the long-term prognosis of patients with lung cancer are not well u n d e r s t o o d [17]. This study describes a 14-year experience with comb i n e d lung resection a n d cardiac operation at The Toronto Hospital. We compare the results of lung resection for m a l i g n a n t disease versus benign disease in an att e m p t to characterize the effect of CPB on the long-term prognosis of patients with lung cancer.
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(Ann Thorac Surg 1996;62:342-7)
Material and Methods Presented at the Third-second Annual Meeting of The Society of Thoracic Surgeons, Orlando, FL, Jan 29-31, 1996. Address reprint requests to Dr Weisel, Division of Cardiovascular Surgery, EN 14-215,The Toronto Hospital, 200 Elizabeth St, Toronto, Ontario M5G 2C2, Canada. © 1996 by The Society of Thoracic Surgeons Published by Elsevier Science lnc
We reviewed the clinical records of all patients who u n d e r w e n t p u l m o n a r y resection and cardiac operation requiring extracorporeal circulation b e t w e e n January 1, 1982 and July 1, 1995. Patients who u n d e r w e n t single or 0003-49751961515.00 Pll S0003-4975(96)00349-9
A n n Thorac Surg 1996;62:342-7
double lung transplantation necessitating CPB (n = 69) were excluded. Follow-up data were collected at the thoracic surgery postoperative clinics a n d were complete for all patients. Follow-up r a n g e d from 1 to 101 m o n t h s (mean, 29 months).
Operative Technique Mediastinoscopy was p e r f o r m e d at the b e g i n n i n g of the operative p r o c e d u r e in 16 of the 18 patients who presented p r e o p e r a t i v e l y with a b n o r m a l chest roentgenograms or with a known diagnosis of malignancy. No N2 disease was f o u n d in any of these 16 patients. The p u l m o n a r y resection was p e r f o r m e d before the institution of CPB in 4 patients, d u r i n g CPB in 19 patients, and after reversal of h e p a r i n t r e a t m e n t in 7 patients. In 23 patients, the cardiac p r o c e d u r e was c o m p l e t e d before the lung resection. Postoperative care was uniform in all patients. Two patients received adjuvant c h e m o t h e r a p y after lung resection. Both of these patients h a d a diagnosis of small cell carcinoma.
Statistical Analysis Statistical analysis was p e r f o r m e d with the BMDP statistical p r o g r a m (BMDP Statistical Software, Los Angeles, CA). Categoric data were evaluated using X2 analysis or Fisher's exact test as appropriate. Continuous variables were analyzed using analysis of variance. Actuarial survival was d e t e r m i n e d using the K a p l a n - M e i e r m e t h o d [18]. The generalized Wilcoxon test was u s e d to c o m p a r e survival b e t w e e n groups. Statistical significance was ass u m e d at p less than 0.05.
Results
Preoperative Data The m e a n age of the 30 patients was 61 + 13 years (range, 17 to 79 years). There were 26 m e n and 4 women. Left ventricular ejection fraction was greater than 0.60 in 9, 0.40 to 0.59 in 16, 0.20 to 0.39 in 5, a n d less than 0.20 in none. T u m o r stage (primary lung cancer) was stage I in 12, stage II in 3, a n d stage IIIa in 2. Other malignancies were p r e s e n t in 4 patients. A b n o r m a l p r e o p e r a t i v e chest r o e n t g e n o g r a m s were detected in 18 patients who p r e s e n t e d with cardiac complaints. Seven patients with known p u l m o n a r y neoplasms were discovered to have substantial u n d e r l y i n g coronary artery disease on the basis of history, and physical examination. These patients s u b s e q u e n t l y und e r w e n t exercise stress tests or thallium scanning before coronary a n g i o g r a p h y a n d consideration of simultaneous coronary revascularization. O n e patient p r e s e n t e d with h e m o p t y s i s and was found to have a tracheal n e o p l a s m and two-vessel coronary artery disease. Four patients u n d e r w e n t cardiac operation a n d h a d p u l m o n a r y lesions detected intraoperatively; the p u l m o n a r y lesion was found to be a benign g r a n u l o m a or e m p h y s e m a t o u s bleb.
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343
12 10
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Operative Data The average aortic cross-clamp time was 54 - 21 m i n u t e s (range, 23 to 106 minutes), and CPB time was 109 + 34 minutes (range, 38 to 158 minutes). The p u l m o n a r y resection consisted of p n e u m o n e c t o m y in 3 patients (10%), lobectomy in 14 (47%), w e d g e resection in 12 (40%), and tracheal resection in I (3%). Twentyfour patients received one or more coronary artery bypass grafts (one in 1, two in 6, three in 10, four in 5, and m o r e than four in 2). Six patients h a d either an aortic (n = 4) or mitral (n = 2) valve replacement. Right or left atrial resection was r e q u i r e d in 2 patients. One patient required a right atrial resection a n d right u p p e r lobe w e d g e resection for metastatic renal cell carcinoma, a n d the second patient r e q u i r e d a left atrial resection for m y x o m a c o m b i n e d with a right lower lobectomy for a metastatic chondrosarcoma. Pathologic examination revealed a malignant lesion in 21 patients: a d e n o c a r c i n o m a (n = 10), s q u a m o u s cell carcinoma (n = 5), small cell carcinoma (n = 2), metastatic renal cell carcinoma (n = 3), a n d metastatic chondrosarcoma (n = 1). The majority of patients (n = 12, 57%) p r e s e n t e d with stage I disease. Two patients were found to have N2 disease at thoracotomy despite negative m e d i a s t i n o s c o p y results. These patients are both alive and disease free at 2 a n d 3 years, respectively. Benign lesions were excised in 9 patients (granulomata or e m p h y s e m a t o u s bleb) (Fig 1). There were two operative deaths. One patient suffered a perioperative stroke and died on postoperative day 15; the second patient died on postoperative day 5 of massive aspiration. Prolonged ventilation (>24 hours) was r e q u i r e d for 4 additional patients, who were all discharged home in satisfactory condition. Only I patient r e q u i r e d r e o p e n i n g for persistent chest tube drainage. This patient had u n d e r g o n e a tracheal resection and double coronary artery bypass. No source of b l e e d i n g was identified at reexploration. One patient suffered a p u l m o n a r y e m b o lus on the third postoperative day. This patient experienced a second p u l m o n a r y e m b o l u s with resultant respiratory arrest. This patient received an inferior vena caval
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R A O ET AL LUNG RESECTION AND CARDIAC OPERATION
Ann Thorac Surg 1 9 9 6 ;6 2: 3 4 2 -7
filter and was eventually discharged home on the 26th postoperative day. One patient who had received five coronary artery bypass grafts and underwent right upper lobectomy required a permanent pacemaker for thirddegree heart block. There were no perioperative myocardial infarctions. The postoperative length of stay for all patients was 12.1 + 7.6 days (median, 10 days; range, 4 to 25 days). For those patients who were discharged from the hospital, the average length of stay was 12.5 +_ 7.8 days (median, 10 days; range, 5 to 25 days).
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There were three late deaths: Two patients died of fatal myocardial infarctions and the third patient died of recurrent malignant disease. Overall actuarial survival was 85% _+ 7% at I year, 85% -+ 7% at 5 years, and 61% _+ 21% at 7 years (Fig 2). Figure 3 compares patients who underwent lung resection for benign disease and those who were found to have a malignant lesion. There was only one death in a patient with benign disease. This patient suffered a fatal myocardial infarction 7 years after bypass operation. There were two late deaths in patients with malignant disease. One patient with metastatic chondrosarcoma presented 3 months after operation with an intracranial lesion and died after an intracerebral hemorrhage. The second patient suffered a fatal myocardial infarction 3 months after bypass. There were 3 patients who developed recurrent disease, but all 3 were alive at follow-up. Of the 2 patients with small cell carcinoma, both were alive and disease free at 2 and 5 years, respectively.
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disease may significantly increase the morbidity of pulmonary resection [1]. In addition, a two-stage procedure has the disadvantages of two anesthetics, two incisions, and a longer overall hospital stay. A single combined procedure may therefore be preferred, with potential economic benefit. Pulmonary resection through a median sternotorny has been shown to result in excellent outcomes [3, 4]. Although the technical feasibility of a simultaneous procedure has been well demonstrated in several small series [5-11], the lack of long-term follow-up in a large series of patients makes it difficult to determine the long-term outcomes of the combined procedure. T h e Effect o f C a r d i o p u l m o n a r y B y p a s s
Cardiopulmonary bypass has been shown to produce several systemic side effects [12-16]. The immunologic effects of CPB are of concern in patients with malignant disease. Cardiopulmonary bypass is known to affect neutrophils and platelets and to result in complement activation. This inflammatory stimulation may be of benefit in patients with malignancies. However, attempts to resect neoplasms during CPB may lead inadvertently to systemic seeding of malignant cells. Blood transfusion is associated with an increased risk of recurrence. In addition, there is a potent immunosuppressive effect of CPB, which may be detrimental to the long-term prognosis of patients with malignancies. A report by Canver and associates [17] demonstrated that cardiac operation in patients with a previously resected cancer gave acceptable results, with a 96% 3-year survival. However, only 1 patient in this series of 46 had a diagnosis of lung cancer. In addition, all patients in this series had undergone a previous "curative" resection of their malignancy and thus, their tumor burden was minimal at the time of cardiac operation. A study by Ulicny and co-workers [9] examined the results of concomitant cardiac and pulmonary procedures. In this series of 19 patients, the authors found a 5-year survival
Ann Thorac Surg 1996;62:342-7
of only 40% in patients with m a l i g n a n t disease, c o m p a r e d with 75% in patients found to have a benign p u l m o n a r y lesion. A similar result was obtained in a larger series r e p o r t e d by Brutel de la Riviere a n d colleagues [10]. In a group of 79 patients who u n d e r w e n t a c o m b i n e d procedure over a 15-year period, the overall survival at 5 years was 42%. The authors found that the 5-year survival was higher in patients who u n d e r w e n t lung resection before CPB (55%) versus those who u n d e r w e n t lung resection after CPB (20%). Unfortunately, this difference failed to achieve statistical significance because of the small n u m ber of patients available for analysis at 5 years. Nevertheless, these results do suggest a potential d e t r i m e n t a l effect of CPB. A r e p o r t by N a r u k e and associates [19] d e m o n s t r a t e d that a m o n g stage I tumors, overall 5-year survival in n o n - s m a l l cell n e o p l a s m s was a p p r o x i m a t e l y 65%. O u r results in patients with malignant disease a p p e a r to be similar to those o b t a i n e d in patients with benign p u l m o n a r y lesions, with an overall 5-year survival of greater than 80%. Thus, it does not a p p e a r that CPB h a d a d e t r i m e n t a l effect on 5-year survival in our series. In addition, the p r e d o m i n a n t cause of late death in our series was cardiac, not recurrence of malignancy. Therefore, patients who u n d e r g o a c o m b i n e d p r o c e d u r e may be at risk for recurrence, but they are just as likely to die of progression of their cardiac disease.
Timing of Lung Resection The timing of the lung resection m a y be i m p o r t a n t for both early a n d late operative outcomes. In addition to the concern r e g a r d i n g systemic m e t a s t a s e s d u r i n g CPB, there is a d a n g e r of b l e e d i n g secondary to anticoagulation therapy. Ulicny and co-workers [9] e x a m i n e d the role of CPB in c o m b i n e d operations and concluded that lung resection during CPB was associated with excessive b l e e d i n g and p u l m o n a r y complications. These authors r e c o m m e n d e d resection after reversal of anticoagulation with p r o t a m i n e sulfate. In our series, 19 (63%) of the patients u n d e r w e n t resection d u r i n g CPB, and only 1 patient suffered from a b l e e d i n g complication requiring reexploration. O u r p r e f e r r e d a p p r o a c h to the stable patient is to perform a preoperative staging mediastinoscopy. We then complete the cardiac p r o c e d u r e a n d remove the aortic cross-clamp. Resection of the p u l m o n a r y lesion is p e r f o r m e d during CPB. C a r d i o p u l m o n a r y b y p a s s facilitates resection of left lower lobe lesions through a m e d i a n sternotomy. Four patients in our series u n d e r w e n t lung resection before the institution of CPB. All 4 of these patients u n d e r w e n t w e d g e resections of p e r i p h e r a l tumors. Three of the 4 were found to have benign disease; the fourth patient was found to have an a d e n o c a r c i n o m a a n d p r o c e e d e d to formal right lower lobectomy after r e p l a c e m e n t of his aortic valve. Seven patients u n d e r w e n t p u l m o n a r y resection after discontinuation of CPB. If there is concern about the patient's ability to w e a n from CPB, we prefer to complete the cardiac p r o c e d u r e and decannulate. If the patient r e m a i n s stable after discontinuation of CPB, we proceed with the p u l m o n a r y resection.
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In patients u n d e r g o i n g valve operations, we prefer to resect the p u l m o n a r y lesion after closure of the pericard i u m to avoid contamination b y respiratory pathogens. In our small series of 6 patients, we did not observe any complications related to infective endocarditis. W e believe that our technique of pericardial closure partially protects against infection due to the presence of a transected airway.
Summary The early outcomes of c o m b i n e d p u l m o n a r y resection and cardiac operation have d e m o n s t r a t e d that this approach is both feasible a n d safe in carefully selected patients. The long-term results of concomitant operation are less well defined because of the lack of a large series of patients available for follow-up. In our series, late death was p r e d o m i n a n t l y r e l a t e d to cardiac causes, which suggests that the adverse effects of CPB on pulm o n a r y malignancies m a y not be an i m p o r t a n t factor w h e n considering a patient for a simultaneous procedure. W h e n faced with a patient with concomitant p u l m o nary a n d cardiac disease, we favor a single-stage comb i n e d procedure. The p u l m o n a r y resection is facilitated by CPB, and we have not o b s e r v e d any increased morbidity from anticoagulation therapy. If the cardiac procedure is difficult or the patient is unstable, the lung resection can be delayed. W e r e c o m m e n d closure of the p e r i c a r d i u m in patients u n d e r g o i n g simultaneous valve operation and lung resection to protect against contamination from a transected airway. In certain high-risk patients, separate staged procedures m a y be the most p r u d e n t course of action. However, in carefully selected patients with concomitant disease, a c o m b i n e d a p p r o a c h can be used with m i n i m a l perioperative morbidity and acceptable long-term results. This study was supported by the Heart and Stroke Foundation of Ontario (HSFO): Dr Rao is a Pharmaceutical Roundtable Fellow of the HSFO; Dr Weisel is a Career Investigator of the HSFO; Dr Cohen is a Surgical Scientist at the Department of Surgery, University of Toronto; and Dr Christakis is a Research Scholar of the HSFO. We thank Ms Joan Ivanov, RN, MSc, for her statistical expertise and assistance with the preparation of the manuscript.
References 1. Thomas P, Giudicelli R, Guillen JC, Fuentes P. Is lung cancer surgery justified in patients with coronary artery disease? Eur J Cardiothorac Surg 1994;8:287-92. 2. Rao TK, Jacobs KH, El-Err AA. Reinfarction following anaesthesia in patients with myocardial infarction. Anaesthesiology 1983;59:499-505. 3. Urschel HC Jr, Razzuk MA. Median sternotomy as a standard approach for pulmonary resection. Ann Thorac Surg 1986;41:130-4. 4. Cooper JD, Nelems JM, Pearson FG. Extended indications for median sternotomy in patients requiring pulmonary resection. Ann Thorac Surg 1978;26:413-9. 5. Piehler JM, Trastek VF, Pairolero PC, et al. Concomitant
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11. 12.
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cardiac and pulmonary operations. J Thorac Cardiovasc Surg 1985;90:662-7. Dalton ML, Parker TM, Mistrot JJ, Bricker DL. Concomitant coronary artery bypass and major noncardiac surgery. J Thorac Cardiovasc Surg 1978;75:621-4. Peters RM, Swain JA. M a n a g e m e n t of the patient with emphysema, coronary artery disease and lung cancer. Am J Surg 1982;143:701-5. Yokoyama T, Derrick MJ, Lee AW. Cardiac operation with associated pulmonary resection. J Thorac Cardiovasc Surg 1993;105:912-6. Ulicny KS Jr, Schmelzer V, Flege JB Jr, et al. Concomitant cardiac and pulmonary operation: the role of cardiopulmonary bypass. Ann Thorac Surg 1992;54:289-95. Brutel de la Riviere A, Knaepen P, Van Swieten H, Ernst J, Van den Bosch J. Concomitant open heart surgery and pulmonary resection for lung cancer. Eur J Cardiothorac Surg 1995;9:310-4. Canver CC, Bhayana JN, Lajos TZ, et al. Pulmonary resection combined with cardiac operations. Ann Thorac Surg 1990;50: 796-9. Christakis GT, Koch JP, Deemar KA, et al. A randomized
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13.
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15. 16. 17.
18. 19.
study of the systemic effects of warm heart surgery. Ann Thorac Surg 1992;54:449-59. Cavarocchi NC, Pluth JR, Schaff HV, et al. Complement activation during cardiopulmonary bypass. J Thorac Cardiovasc Surg 1986;91:252-8. Moore FD, Warner KG, Assousa S, et al. The effect of complement activation during cardiopulmonary bypass. Ann Surg 1988;208:95-103. Butler J, Rocker GM, Westaby S. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1993;55:552-9. Colman RW. Platelet and neutrophil activation in cardiopulmonary bypass. Ann Thorac Surg 1990;49:32-4. Canver CC, Mazzin CAS, Plume SK, Nugent WC. Should a patient with a treated cancer be offered an open heart operation? Ann Thorac Surg 1993;53:1202-4. Kaplan EL, Meier P. Non-parametric estimations from incomplete observations. J Am Stat Assoc 1958;53:457-81. Naruke T, Goya T, Tsuchiya R, Suemasu K. Prognosis and survival in resected lung carcinoma based on the new international staging system. J Thorac Cardiovasc Surg 1988; 96:440-7.
DISCUSSION DR PETER C. PAIROLERO (Rochester, MN): I thank Dr Rao for his excellent presentation. The issue of compromised survival for patients with lung cancer after concomitant pulmonary and cardiac operations is not new. Peters first suggested this association as early as 1982, w h e n he suggested that alterations in the i m m u n e mechanism occurred after extracorporeal circulation that accelerated malignant disease. Since then, others, including our group, have suggested that it is less a matter of reduced immunocompetency and more a situation of incomplete cancer staging through a median sternotomy incision. In our series of 30 patients with lung cancer presented before this Society 2 years ago, overall 5-year survival after concomitant pulmonary and cardiac operations was 35%. This is in marked contrast to the 64% five-year survival reported in the present study for patients with malignant disease. Equally as important, survival in our concomitant patients was not significantly affected by the stage of the disease, even though more than 75% of our patients were presumed to have stage I disease. Our observation of reduced survival was also in marked contrast to the survival observed in another of our patient groups, who had cardiac operations followed by staged pulmonary resections for lung cancer within the following year. Five-year survival for our staged patients was 53%. Why the differences? Well, for one thing, the n u m b e r of patients in both the Toronto group and our group is small, and this could easily explain the differences. We, however, concluded that lymph node evaluation was not as complete in our patients undergoing concomitant operations because of the limitations of exposure imposed by the median sternotomy. In fact, we concluded that some of our stage I concomitant patients were actually occult stage IIL Recognizing the limitations imposed by sternotomy, Dr Rao suggested, and I entirely agree, that mediastinoscopy be performed before an elective cardiac operation in all patients with known lung cancer. But what about the patients found to have lung cancer during the cardiac surgical procedure? I would like to ask several questions. What does the Toronto group recomm e n d be done at the time of sternotomy to ensure adequate staging of the mediastinum if mediastinoscopy has not been
previously done? Specifically, how do they evaluate the subcarinal lymph nodes? The concern, of course, is that subcarinal lymph nodes are not sampled. Second, did their patients have lymphadenectomy or simply lymph node biopsy of the various stations? Their 5-year cancer survival of 64% is excellent and suggests a stage I disease pattern. This is even more significant w h e n you realize that 30% of their primary cancer patients had either stage Ii or stage III disease and that another 10% of their patients had small cell lung cancers. DR RAO: Dr Pairolero has raised a n u m b e r of important issues. First, there is the importance of the timing of the lung resection vis-a-vis the institution of cardiopulmonary bypass. A large European study by Brutel de la Riviere and associates examined 79 patients who underwent concomitant operations over a 15-year period. There was a small, statistically nonsignificant improvement in survival in those patients who underwent lung resection before cardiopulmonary bypass. Unfortunately, their series and ours lack the statistical power to detect a difference in survival if one exists. Their finding does raise a concern, however, about the possible detrimental effects of cardiopulmonary bypass on the long-term prognosis of these patients. The second point concerned the adequacy of preoperative staging during a combined procedure. Cervical mediastinoscopy is a routine procedure at our institution. Ideally, a patient who presents with concomitant disease is adequately staged preoperatively and intraoperatively. In the unfortunate event that a "surprise" lesion is found at cardiac operation, there are a n u m b e r of options. We prefer to perform a wedge excision for pathologic confirmation of malignancy. If the patient is unstable during the operation, we would complete the cardiac procedure and proceed with complete tumor staging postoperatively, with the potential for a second, staged procedure. Alternatively, if the patient is stable, we would proceed to open the posterior pericardium and mobilize the right pulmonary artery, allowing an extensive evaluation of the subcarinal space. If no nodal disease were found, we would complete a formal cancer resection as clinically indicated.
Ann Thorac Surg 1996;62:342-7
DR WILLIAM MITCHEL SEE (Columbia, MO): Doctor Rao, you certainly have had very, good results. I am impressed that the distribution of stage I patients was very high relative to what we expect. In Missouri, we have performed 20 combined procedures and several that we staged, as Dr Pairolero suggested. One of the difficult problems I have that is not addressed in this study is the pleural space. We are still using cold cardioplegia and topical cooling, and nearly all of my patients have left lower lobe atelectasis. Their chest roentgenograms do not normalize for about 6 or 8 weeks. It has been a real problem for me in performing a lobectomy, which has its own space problems, directly after a cardiac operation, when you need to have all of the lung reexpanded. I also have been reluctant to pursue lower lobectomies simply because I am not in favor of performing them during cardiopulmonary bypass. Instead, I finish the cardiac operation and then, only if everything is perfect, will I consider an upper lobectomy. I would like to ask you about your pleural space problems. Does this combined lung resection and coronary artery bypass procedure dissuade you from using the internal mammary artery as a conduit? Do you try to stay out of that pleural space? D R RAO: We have found that topical cooling leads to an increased risk of phrenic nerve injury and diaphragmatic paral-
RAO ET AL [,UNG RESECTION AND CARDIAC OPERATION
ysis, which may predispose to pulmonary complications postoperatively. Our incidence of pleural space complications decreased significantly after we a b a n d o n e d the use of topical slush. Four patients had emphysematous lesions detected intraoperatively, which may have compromised the use of a m a m m a r y artery graft. These blebs were successfully removed with wedge excisions to allow proper placement of the left internal mammary artery. Thus, we do not believe that a combined procedure precludes the use of a m a m m a r y artery. D R SHAF KESHAVJEE (Toronto, Ontario, Canada): One of the
other options that we use for unexpected intraoperative findings is a diagnostic wedge resection. I believe that the low mortality and low morbidity results that Dr Rao reported reflect this clinical judgment. In the case of a complex valvular and bypass operation, for example, we would do a wedge resection of the lesion for diagnosis. W h e n the patient recovers from the cardiac procedure, we would bring him back for complete radiologic imaging and mediastinoscopy, followed by lung resection. We emphasize, however, that "unexpected" pulmonary pathologic findings can be avoided if the preoperative chest roentgenogram is reviewed.
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